Cross talk of cAMP and flavone in regulation of cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel and Na+/K+/2Cl- cotransporter in renal epithelial A6 cells
Cross talk of cAMP and flavone in regulation of cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel and Na+/K+/2Cl- cotransporter in renal epithelial A6 cells
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DOI：
10.1016/j.bcp.2003.10.026
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发表时间：
2004-02-15
影响因子：
5.8
通讯作者：
Marunaka, Y
中科院分区：
文献类型：
--
作者：
Niisato, N;Nishino, H;Marunaka, Y
我们已经报道，在肾上皮A6细胞中，黄酮通过激活囊性纤维化跨膜传导调节因子（CFrR）Cl-通道和/或Na+/K+/2Cl（-）协同转运体来刺激跨上皮Cl-分泌。另一方面，已经确定cAMP激活CFrR Cl-通道和Na+/K+/2Cl（-）协同转运蛋白。然而，没有关于cAMP和黄酮之间的相互作用对CFrR Cl-通道和Na+/K（+）2Cl（-）协同转运蛋白的刺激的信息。为了阐明cAMP和黄酮类化合物之间的相互作用，我们研究了在基础和cAMP刺激条件下，黄酮类化合物（芹菜素、毛地黄黄酮、山奈酚和槲皮素）对肾上皮A6细胞CFFR Cl-通道和Na+/K+/2Cl（-）协同转运体的调节机制。在基础（cAMP未刺激）条件下，这些黄酮通过激活Na+/K+/ 20-共转运体刺激Cl-分泌，但对CFrR Cl-通道活性无显著影响。另一方面，这些黄酮降低cAMP刺激的Na+/K+/2Cl（-）共转运蛋白的活性，而对CFrR Cl-通道活性没有任何显著影响。有趣的是，在基础条件下黄酮诱导的Cl-分泌水平与cAMP刺激条件下相同。结果表明，虽然cAMP和黄酮类化合物都能激活Na+/K+/2Cl（-）共转运体，但黄酮类化合物对Na+/K+/2Cl（-）共转运体的作用比cAMP更强。(C)2003年爱思唯尔公司All rights reserved.
We have reported that in renal epithelial A6 cells flavones stimulate the transepithelial Cl- secretion by activating the cystic fibrosis transmembrane conductance regulator (CFrR) Cl- channel and/or the Na+/K+/2Cl(-) cotransporter. On the other hand, it has been established that cAMP activates the CFrR Cl- channel and the Na+/K+/2Cl(-) cotransporter. However, no information is available on the interaction between cAMP and flavones on stimulation of the CFrR Cl- channel and the Na+/K(+)2Cl(-) cotransporter. To clarify the interaction between cAMP and flavones, we studied the regulatory mechanism of the CFFR Cl- channel and the Na+/K+/2Cl(-) cotransporter by flavones (apigenin, luteolin, kaempherol, and quercetin) under the basal and cAMP-stimulated conditions in renal epithelial A6 cells. Under the basal (cAMP-unstimulated) condition, these flavones stimulated the Cl- secretion by activating the Na+/K+/ 20- cotransporter without any significant effects on the CFrR Cl- channel activity. On the other hand, these flavones diminished the activity of the cAMP-stimulated Na+/K+/2Cl(-) cotransporter without any significant effects on the CFrR Cl- channel activity. Interestingly, the level of the flavone-induced Cl- secretion under the basal condition was identical to that under the cAMP-stimulated condition. Based on these results, it is suggested that although both cAMP and flavones activate the Na+/K+/2Cl(-) cotransporter, these flavones have more powerful effects than cAMP on the Na+/K+/2Cl(-) cotransporter. (C) 2003 Elsevier Inc. All rights reserved.